Repeated, transient lactate exposure does not 'precondition' rat myocardium

The precise mechanism of the cardioprotective effect of ischemic preconditioning (IPC) is still unclear, although various mechanisms have been suggested, including activation of ATP-dependent potassium (K(ATP)) channels by adenosine and protein kinase C as well as increased expression of heat shock protein (HSP). Increasing evidence suggests that lactate, which accumulates during IPC periods, can activate several of these 'triggers' of preconditioning. We tested whether repeated exposure to lactate, producing tissue lactate concentrations similar to those during brief ischemic periods, could contribute to IPC benefits. Five isolated rat hearts were subjected to a previously reported IPC protocol composed of two 5-min ischemia-reperfusion cycles; another five hearts served as controls; and six hearts underwent a 'lactate-preconditioning' protocol, consisting of two 5-min exposures to 15 mM lactate and two 5-min periods of reflow with a lactate-free buffer. Subsequently all hearts underwent 30 min of normothermic, total ischemia followed by 30 min of reflow at a constant perfusion pressure of 80 mmHg (1 mmHg = 133.3 Pa). Lactate exposure resulted in tissue lactate levels similar to those during ischemia in ischemia-preconditioned hearts (10.5 ± 0.6 versus 10.5 ± 1.2 μmol/g wet weight, mean ± SEM). However, the recovery of left ventricular developed pressure (DevP) following 30 min of total ischemia was significantly higher in the IPC hearts than in either the control or lactate-exposed hearts, reaching 56.8 ± 3.4, 14.2 ± 6.8, and 9.5 ± 3.6%, respectively, of the baseline values. There was no significant difference between lactate-preconditioned and control hearts. End-diastolic pressure (EDP) was significantly lower during reperfusion in TPC hearts than in lactate-exposed and control hearts, with no significant differences between the latter two groups (36.2 ± 3.5, 82.0 ± 2.9, and 81.2 ± 8.5 mmHg, respectively). In contrast with the proposed hypothesis, repeated, transient lactate exposure resulting in tissue lactate levels similar to ischemic preconditioning did not improve contractile recovery after a prolonged ischemic period in this model.